Showing papers by "Robert S. Smith published in 2012"

Myeloma-Specific Multiple Peptides Able to Generate Cytotoxic T Lymphocytes: A Potential Therapeutic Application in Multiple Myeloma and Other Plasma Cell Disorders

Abstract: Purpose: The efficacy of peptide vaccines may be enhanced by stimulating immune cells with multiple peptides derived from distinct tumor-associated antigens. We have evaluated the heteroclitic XBP1-US 184–192 (YISPWILAV), heteroclitic XBP1-SP 367–375 (YLFPQLISV), native CD138 260–268 (GLVGLIFAV), and native CS1 239–247 (SLFVLGLFL) peptides, which have strong HLA-A2 affinity and immunogenicity in combination, for their ability to elicit multiple myeloma antigen–specific responses. Experimental Design: Multipeptide-specific cytotoxic T lymphocytes (MP-CTL) were generated by the stimulation of CD3 + T lymphocytes from HLA-A2 + individuals with either autologous mature dendritic cells or T2 cells pulsed with a cocktail of these four peptides. Results: The peptide cocktail did not compromise tumor antigen–specific activity of CTLs. MP-CTLs displayed increased total, effector memory (CCR7 − CD45RO + ), and activated (CD69 + ) CD3 + CD8 + T lymphocytes. In addition, MP-CTL showed IFN-γ production, cell proliferation, and cytotoxicity against HLA-A2 + multiple myeloma cells, including cells of HLA-A2 + patients with multiple myeloma. Importantly, MP-CTLs showed specific responses in functional assays to each relevant peptide but not to an irrelevant HLA-A2–specific CMV pp65 (NLVPMVATV) peptide. Conclusions: These results highlight the potential therapeutic application of vaccination with a cocktail of HLA-A2–specific peptides to induce CTLs with a broad spectrum of immune responses against multiple myeloma antigens. Clin Cancer Res; 18(17); 4850–60. ©2012 AACR .